Background: Identifying risk factors of cardiovascular events is crucial for stroke prevention and they can be used as predictive factors of stroke outcomes.In this study, it is to evaluate the risk factors that predict outcomes of acute non-cardioembolic ischemic stroke in patients stratified by Essen Stroke Risk Score (ESRS).Methods: A retrospective study was carried out in acute non-cardioembolic ischemic stroke patients in a Chinese tertiary-care teaching hospital. ESRS stratification and factors that might influence the outcomes of stroke, as indicated by fatal or non-fatal combined vascular events of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage, were documented. Univariate analysis and multivariable regression analysis was used to identify independent predictors of stroke outcomes.Results: A total of 878 patients with acute non-cardioembolic ischemic stroke who completed a mean follow-up of 5.2 years were enrolled, and 163 patients experienced at least one component of the combined vascular event. In patients with an ESRS ≤ 3, age ≥ 65 years (OR , 2.935; 95% CI 1.625-5.301, P < 0.001) and clopidogrel treatment (OR , 1.685 ; 95% CI , 1.026-2.768; P = 0.041) were significantly associated with stroke outcomes. In patients with an ESRS > 3, age ≥ 65 years (OR , 2.107, 95% CI , 1.208-3.673 ; P = 0.008) and history of diabetes (OR , 1.465 ; 95% CI , 1.041-2.062 ; P = 0.027) were risk factors for stroke outcomes , whereas clopidogrel treatment (OR , 0.542; 95% CI , 0.356-0.824; P = 0.003) was a protective factor for stroke outcomes.Conclusions: According to this study, clopidogrel treatment, blood pressure control, and glycemic control are protective factors for stroke outcomes in high-risk patients (ESRS>3).